The purpose of this study is to evaluate detrusor responses to centrally administered drugs and to determine the existence and the anatomical relationship to the pontine micturition center of central nervous system cholinergic receptors capable of modulation of detrusor function. The drugs selected for study are bethanechol, pilocarpine, physostigmine, oxytremorine, and atropine sulfate. Peripheral effects of these drugs are also evaluated to demonstrate the relative contribution of both the isolated central and peripheral sites of action as well as the interaction of the drugs as each site. The cross perfusion technique used in this experiment utilizes two animals in which the carotid arteries and external jugular veins of each are connected to the femoral arteries and veins of the opposite animal using polyethylend tubing. Other arteries and vens going to the brain are ligated. This allows isolated perfusion of either the central nervous system or the peripheral nervous system with each drug. The measurement of responses to drugs will be done using combined cystometrych the carotid arteries and external jugular veins of each are connected to the femoral arteries with simultaneous periurethral EMG. Twelve preliminary studies have been performed as well as two additional studies to determine the time of onset of action. Six animals receiving central bethanechol had a mean preinfusion bladder capacity of 165 cc and a mean postingusion capacity of 18cc. The postingusion bladder capacity following central atropine was twice the preinfusion volume. Bethanechol produced a rise in peak detrusor pressure while atropine produced a decrease in pressure. Central physostigmine showed no effect in two animals and central oxytremarine produced asystole in two animals. Central bethanechol produced a detrusor contraction 15 seconds aftefunction. The coordinated function of the bladder and urethra has been demonstrated to be organized in the pons and modulated by multiple areas rostral to the pons. Data from this study will provide a basis for extensive investigation of the central nervous system control of voiding in future proposals. Successful pharmacologic therapy of voiding dysfunctions in the aged will be dependent on drugs having actions on the central nervous system centers which modulate voiding rather than peripheral actions at the pelvic ganglia and neromuscular junction.